新型6-杂芳基-3-肼基哒嗪衍生物的合成及其降压活性
Synthesis and antihypertensive activity of new 6-heteroaryl-3-hydrazinopyridazine derivatives.
作者信息
Steiner G, Gries J, Lenke D
出版信息
J Med Chem. 1981 Jan;24(1):59-63. doi: 10.1021/jm00133a013.
The synthesis and pharmacological activity of new 6-heteroaryl-3-hydrazinopyridazines with antihypertensive action are described. The introduction of pyrrole, pyrazole, imidazole, triazole, tetrazole, thiophene, indole, and carbazole heterocyclic rings into the 6 position of the pyridazine nucleus has been carried out by three different methods of synthesis. The hypotensive action has been examined on normotensive and spontaneously hypertensive rats by comparison with dihydralazine (I). 6-Imidazol-1-yl derivatives have proved particularly active. Of these derivatives, 3-hydrazino-6-(2-methylimidazol-1-yl)pyridazine (7c) achieves 4.9 times the activity of dihydralazine when administered orally to spontaneously hypertensive rats. The LD50 values of 7c and dihydralazine are very similar.
描述了具有抗高血压作用的新型6-杂芳基-3-肼基哒嗪的合成及其药理活性。通过三种不同的合成方法，将吡咯、吡唑、咪唑、三唑、四唑、噻吩、吲哚和咔唑杂环引入到哒嗪核的6位。通过与双肼屈嗪（I）比较，研究了其对正常血压大鼠和自发性高血压大鼠的降压作用。已证明6-咪唑-1-基衍生物具有特别高的活性。在这些衍生物中，3-肼基-6-(2-甲基咪唑-1-基)哒嗪（7c）对自发性高血压大鼠口服给药时，活性是双肼屈嗪的4.9倍。7c和双肼屈嗪的半数致死量值非常相似。
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